Sequential therapies for Crohn's disease: optimizing conventional and biologic strategies.

The current guidelines for the management of Crohn's disease (CD) suggest a stepwise approach to treatment according to the severity of clinical presentation. The use of tumor necrosis factor (TNF) antagonists are currently reserved for patients who do not respond to conventional nonbiological therapies such as corticosteroids and immunosuppressants. However, as TNF-alpha antagonists have the potential to produce mucosal healing in CD, earlier more aggressive treatment with biologics has been advocated. Anti-TNF therapy may be most beneficial in the early stages of inflammatory disease, before patients develop complications such as fibrostenotic or penetrating disease. Thus, the use of the more aggressive "top-down" strategy involving early introduction of biologics has been explored. Emerging data suggest that earlier use of biological therapy is associated with improved clinical outcomes and potential disease-modifying effects. Future studies are warranted and will likely lead to the expanded use of such agents in the treatment of CD.